6VPY

I33M (I3.2 mutant from CH103 Lineage)

  • Classification: IMMUNE SYSTEM
  • Organism(s): Homo sapiens
  • Expression System: Homo sapiens
  • Mutation(s): No 

  • Deposited: 2020-02-04 Released: 2020-07-15 
  • Deposition Author(s): Fera, D., Zhou, J.
  • Funding Organization(s): amfAR, The Foundation for AIDS Research, National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID), National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS), Department of Energy (DOE, United States), National Institutes of Health/Office of Research Infrastructure Programs (NIH/ORIP)

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.36 Å
  • R-Value Free: 0.223 
  • R-Value Work: 0.185 
  • R-Value Observed: 0.187 

wwPDB Validation   3D Report Full Report

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This is version 1.3 of the entry. See complete history


Literature

The Effects of Framework Mutations at the Variable Domain Interface on Antibody Affinity Maturation in an HIV-1 Broadly Neutralizing Antibody Lineage.

Zhou, J.O.Zaidi, H.A.Ton, T.Fera, D.

(2020) Front Immunol 11: 1529-1529

  • DOI: https://doi.org/10.3389/fimmu.2020.01529
  • Primary Citation of Related Structures:  
    6VPY

  • PubMed Abstract: 

    Understanding affinity maturation of antibodies that can target many variants of HIV-1 is important for vaccine development. While the antigen-binding site of antibodies is known to mutate throughout the co-evolution of antibodies and viruses in infected individuals, the roles of the mutations in the antibody framework region are not well understood. Throughout affinity maturation, the CH103 broadly neutralizing antibody lineage, from an individual designated CH505, altered the orientation of one of its antibody variable domains. The change in orientation was a response to insertions in the variable loop 5 (V5) of the HIV envelope. In this study, we generated CH103 lineage antibody variants in which residues in the variable domain interface were mutated, and measured the binding to both autologous and heterologous HIV-1 envelopes. Our data show that very few mutations in an early intermediate antibody of the lineage can improve binding toward both autologous and heterologous HIV-1 envelopes. We also crystallized an antibody mutant to show that framework mutations alone can result in a shift in relative orientations of the variable domains. Taken together, our results demonstrate the functional importance of residues located outside the antigen-binding site in affinity maturation.


  • Organizational Affiliation

    Department of Chemistry and Biochemistry, Swarthmore College, Swarthmore, PA, United States.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
I33M light chainA [auth B],
D [auth L]
213Homo sapiensMutation(s): 0 
UniProt
Find proteins for Q8N355 (Homo sapiens)
Explore Q8N355 
Go to UniProtKB:  Q8N355
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8N355
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
I33M heavy chainB [auth A],
C [auth H]
232Homo sapiensMutation(s): 0 
UniProt
Find proteins for Q6GMX6 (Homo sapiens)
Explore Q6GMX6 
Go to UniProtKB:  Q6GMX6
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ6GMX6
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.36 Å
  • R-Value Free: 0.223 
  • R-Value Work: 0.185 
  • R-Value Observed: 0.187 
  • Space Group: P 65
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 131.605α = 90
b = 131.605β = 90
c = 104.908γ = 120
Software Package:
Software NamePurpose
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing
Cootmodel building
PHENIXrefinement
PDB_EXTRACTdata extraction

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
amfAR, The Foundation for AIDS ResearchUnited States109502-61-RKVA
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United States1R15AI150484 - 01A1
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesP30 GM124165
Department of Energy (DOE, United States)United StatesDE-AC02-06CH11357
National Institutes of Health/Office of Research Infrastructure Programs (NIH/ORIP)United StatesS10OD021527

Revision History  (Full details and data files)

  • Version 1.0: 2020-07-15
    Type: Initial release
  • Version 1.1: 2020-08-19
    Changes: Database references
  • Version 1.2: 2020-09-09
    Changes: Author supporting evidence, Data collection
  • Version 1.3: 2023-10-11
    Changes: Data collection, Database references, Refinement description